Insulin-Treatment of Diabetic Rats: Effects on Duodenal Calcium Absorption

Abstract

We tested the hypothesis that depressed duodenal calcium absorption in the streptozotocin diabetic rat is the consequence of diabetes rather than nephrotoxicity of the diabetogenic agent causing abnormal renal vitamin D metabolism. We treated streptozotocin diabetic rats with insulin and compared their duodenal calcium transport response with that of untreated diabetics and matched controls. Insulin treatment restored depressed calcium transport of diabetics to control levels in in vivo studies and significantly increased calcium transport in vitro. Previous studies showed that even in uncontrolled diabetes the mucosa retains the ability to respond to an end organ stimulus enhancing calcium transport: 1,25-dihydroxycholecalciferol corrects the defect, but vitamin D and 25-hydroxycholecalciferol are ineffective. Since 1,25-dihydroxycholecalciferol is synthesized in the kidney, these findings, in conjunction with the current study, are consistent with the association of experimental diabetes with a renal defect depressing synthesis of 1,25-dihydroxycholecalciferol. Since insulin treatment restores duodenal calcium transport, the renal defects is unlikely to be caused by streptozotocin nephrotoxicity.

MECHANISMS IN ENDOCRINOLOGY: Mechanisms and evaluation of bone fragility in type 1 diabetes mellitus

“…Both animals with experimentally induced diabetes and patients with T1DM demonstrate similar metabolic bone profiles, namely, impaired bone formation and low levels of osteocalcin/bone-specific alkaline phosphatase, whereas it is less clear whether increased bone resorption also occurs. Employing short-term (2-week) animal models of streptozotocin diabetes, the low BMD observed in insulinopenic diabetes was earlier explained by secondary hyperparathyroidism and increased bone resorption resulting from a negative calcium balance (impaired intestinal calcium absorption; hypercalciuria) (69,70). Using more appropriate animal models of chronic diabetes (8-10 weeks), and employing time-spaced tetracycline labelled bone histomorphometry, bone formation and resorption were found to be markedly suppressed (71,72,73,74).…”

Evidence for the presence of insulin binding sites in isolated rat intestinal epithelial cells

“…These discrepancies may be due to the fact that most studies were performed in vivo and that insulin does not seem to stimulate, in the intestine, the uptake of glucose and amino-acids [4,7,8,15,19,26], which is one of the specific actions of insulin on target-tissues [19, 24, ]. However, when injected in vivo to diabetic rats, insulin restores to normal the depressed Ca 2+ transport [40]. In addition, insulin injected to control rats stimulates the brush border enzymes activities such as lactase and sucrase [29].…”

Effects of Diabetes on Calcium-Binding Protein in the Cecum and Colon of the Rat

“…Cecal and colonic CaBP are also vitamin D dependent [8]. Dia betic rats show other evidence for vitamin D deficiency including decreased duodenal [3,15,16] and cecal and colonic [9] calcium transport in comparison with controls. The depression of calcium transport in diabetes is also the result of deficiency of l,25-(OH)2D since the transport defect is corrected by ad ministration of l,25-(OH)2D [17], and by in sulin treatment [16], which restores 1,25-(OH)2D to normal in diabetes [1], Based on our previous study of vitamin D metabolites in diabetes [1], the present study shows that CaBP of cecum and colon re sponds to lower levels of serum 1,25-dihydroxyvitamin D in the diabetic state.…”